Search

Search Results

• 1. [Article] ImpL2 Represses Insulin Signaling in Response to Hypoxia

  xiii, 56 p. : ill. (some col.)

  Citation × Citation Citation Abstract Copy Title: ImpL2 Represses Insulin Signaling in Response to Hypoxia Author: Allee, John Paul, 1970- Year: 2011 xiii, 56 p. : ill. (some col.) Title: ImpL2 Represses Insulin Signaling in Response to Hypoxia Author: Allee, John Paul, 1970- Year: 2011 xiii, 56 p. : ill. (some col.) Close

• 2. [Article] Cullin-3 Targets Cyclin E for Ubiquitination and Controls S Phase in Mammalian Cells

  Cyclin E is an unstable protein that is degraded in a ubiquitin- and proteasome- dependent pathway. Two factors stimulate cyclin E ubiquitination in vivo: when it is free of its CDK partner, and when it ...

  Citation × Citation Citation Abstract Copy Title: Cullin-3 Targets Cyclin E for Ubiquitination and Controls S Phase in Mammalian Cells Author: Singer, Jeffrey D., Gurian-West, Mark, Clurman, Bruce, Roberts, James M. Year: 1999 Cyclin E is an unstable protein that is degraded in a ubiquitin- and proteasome- dependent pathway. Two factors stimulate cyclin E ubiquitination in vivo: when it is free of its CDK partner, and when it is phosphorylated on threonine 380. We pursued the first of these pathways by using a two-hybrid screen to identify proteins that could bind only to free cyclin E. This resulted in the isolation of human Cul-3, a member of the cullin family of E3 ubiquitin–protein ligases. We found that Cul-3 was bound to cyclin E but not to cyclin E-Cdk2 complexes in mammalian cells, and that overexpression of Cul-3 increased ubiquitination of cyclin E but not other cyclins. Conversely, deletion of the Cul-3 gene in mice caused increased accumulation of cyclin E protein, and had cell-type-specific effects on S-phase regulation. In the extraembryonic ectoderm, in which cells undergo a standard mitotic cycle, there was a greatly increased number of cells in S phase. In the trophectoderm, in which cells go through endocycles, there was a block to entry into S phase. The SCF pathway, which targets cyclins for ubiquitination on the basis of their phosphorylation state, and the Cul-3 pathway, which selects cyclin E for ubiquitination on the basis of its assembly into CDK complexes, may be complementary ways to control cyclin abundance. Title: Cullin-3 Targets Cyclin E for Ubiquitination and Controls S Phase in Mammalian Cells Author: Singer, Jeffrey D., Gurian-West, Mark, Clurman, Bruce, Roberts, James M. Year: 1999 Cyclin E is an unstable protein that is degraded in a ubiquitin- and proteasome- dependent pathway. Two factors stimulate cyclin E ubiquitination in vivo: when it is free of its CDK partner, and when it is phosphorylated on threonine 380. We pursued the first of these pathways by using a two-hybrid screen to identify proteins that could bind only to free cyclin E. This resulted in the isolation of human Cul-3, a member of the cullin family of E3 ubiquitin–protein ligases. We found that Cul-3 was bound to cyclin E but not to cyclin E-Cdk2 complexes in mammalian cells, and that overexpression of Cul-3 increased ubiquitination of cyclin E but not other cyclins. Conversely, deletion of the Cul-3 gene in mice caused increased accumulation of cyclin E protein, and had cell-type-specific effects on S-phase regulation. In the extraembryonic ectoderm, in which cells undergo a standard mitotic cycle, there was a greatly increased number of cells in S phase. In the trophectoderm, in which cells go through endocycles, there was a block to entry into S phase. The SCF pathway, which targets cyclins for ubiquitination on the basis of their phosphorylation state, and the Cul-3 pathway, which selects cyclin E for ubiquitination on the basis of its assembly into CDK complexes, may be complementary ways to control cyclin abundance. Close